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Background <p>Hepatocellular carcinoma (HCC) remains difficult to treat due to poor drug bioavailability and systemic toxicity of sorafenib (SFB) therapy.</p> Method <p>To address these challenges, PEG-coated iron oxide nanoparticles (PIO) combined with cerium oxide nanoparticles (CeO₂ NPs) were employed to prepare the sorafenib nanococktail (SNC), forming a multifunctional nanoplatform for targeted delivery.</p> Results <p>The optimized SNC exhibited nanoscale size of 124 nm, uniform distribution, and high drug encapsulation efficiency. In vitro release studies confirmed controlled and pH-responsive release, with enhanced drug diffusion under acidic tumor-like conditions. Antioxidant evaluation showed sustained ROS-scavenging activity by CeO₂ NPs, supporting therapeutic synergy. Pharmacokinetic and biodistribution studies demonstrated significantly higher C<sub>max</sub>, prolonged half-life, and improved hepatic retention for SNC compared to SFB suspension. Two-way ANOVA confirmed highly significant differences between SNC and SFB suspension (<i>P</i>&lt; 0.0001), while histopathological analysis revealed preserved hepatic architecture in SNC-treated rats relative to suspension.</p> Conclusion <p>These findings establish SNC as a safe and effective nanocarrier system, capable of improving sorafenib bioavailability and reducing toxicity for enhanced HCC management.</p> Graphical Abstract <p></p>

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Engineered Multifunctional Nanococktail of Sorafenib for Targeted Therapy in Hepatic Cancer: In Vivo Study

  • 期刊论文

  • 发表日期：

    2026年7月16日

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  • Farin Dange,
  • Babita Agarwal,
  • Namdev More,
  • Prabhakar Panzade,
  • Pavan Rathi,
  • Sachin Jagdale

摘要

Background

Hepatocellular carcinoma (HCC) remains difficult to treat due to poor drug bioavailability and systemic toxicity of sorafenib (SFB) therapy.

Method

To address these challenges, PEG-coated iron oxide nanoparticles (PIO) combined with cerium oxide nanoparticles (CeO₂ NPs) were employed to prepare the sorafenib nanococktail (SNC), forming a multifunctional nanoplatform for targeted delivery.

Results

The optimized SNC exhibited nanoscale size of 124 nm, uniform distribution, and high drug encapsulation efficiency. In vitro release studies confirmed controlled and pH-responsive release, with enhanced drug diffusion under acidic tumor-like conditions. Antioxidant evaluation showed sustained ROS-scavenging activity by CeO₂ NPs, supporting therapeutic synergy. Pharmacokinetic and biodistribution studies demonstrated significantly higher Cmax, prolonged half-life, and improved hepatic retention for SNC compared to SFB suspension. Two-way ANOVA confirmed highly significant differences between SNC and SFB suspension (P< 0.0001), while histopathological analysis revealed preserved hepatic architecture in SNC-treated rats relative to suspension.

Conclusion

These findings establish SNC as a safe and effective nanocarrier system, capable of improving sorafenib bioavailability and reducing toxicity for enhanced HCC management.

Graphical Abstract